The specific aim of this Core is to use the power of twin and sibling pairs, coupled with SNP and microsatellite genotyping at candidate loci, to establish the significance or effect of such loci, in particular to understand whether allelic variation at such loci influences autonomic function in either the sympathetic or parasympathetic branches. The autonomic nervous system is the key second-to-second regulator of the circulation, and hence of blood pressure. Autonomic activity is deranged not only in patients with established hypertension, but also in their still-normotensive offspring; thus, autonomic traits are valuable as ?intermediate phenotypes? (O?Connor et al, 2000; Dao et al, 1998; Kailasam et al, 1996, 2000; Lacy et al, 1998; Brinton et al, 1996; Song et al, 2000) in hypertension, a common disease with non-Mendelian (complex) inheritance (Schork and Lander, 1994). Since Human phenotyping plays a role that is largely hypothesis generating (rather than hypothesis testing), and since the materials from Human phenotyping (biological samples, DNA, phenotypes, genotypes) now flow systematically to all Projects and Cores (see Diagram), the previous Project on Human phenotyping has been retooled to form new Core C, ?Human phenotyping? (O?Connor and Ziegler). The previous leader of pedigree phenotyping has now moved on to a new series of additional clinical duties in nephrology (wards, consultations, and clinics) at the San Diego VA Medical Center. This change should facilitate interactions among all Projects and Cores. Core C utilizes the San Diego Twin Project <http://medicine.ucsd.edu/hypertension/twins.html>, which has already recruited n=245 nuclear families based on human MZ and DZ twin pairs (also ascertaining available sibs and parents), phenotyped and genotyped as outlined below, as well as an additional n=69 nuclear families based on sib trios. These nuclear families already give rise to n=573 sib pairs. Twin pairs allow estimation of heritability (h2), which in turn allows us to determine the tractability of any human trait (biochemical or physiological) to genetic investigation. Parental DNA is available on these twinships and sibships (from approximately 45% of parents). The previous phenotyping Project also ascertained n=69 nuclear families based on probands with essential hypertension (first degree relatives studied; average sibship size 3 [offspring of the hypertensive patient]). Genomic DNAs from these sibling pairs, and parents, have already been subjected to a n=777 microsatellite (approximately 5 cM) genome scan, performed by James L. Weber at the NHLBI?s Mammalian Genotyping Service at Marshfield Clinic. This genome scan was completed in April of 2004. Major results emerging from studies employing the human subjects (especially twin pairs) studied by Core C are presented in the overall Preamble to the HL58120 renewal application.